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Course and Treatment of Depression During Pregnancy and the Postpartum Period : Lessons Learned Across Two Decades

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Course and Treatment of Depression During Pregnancy and the Postpartum Period : Lessons Learned Across Two Decades Course and Treatment of Depression during Pregnancy and the Postpartum Period : Lessons Learned Across Two Decades Lee S. Cohen, MD Director, Ammon-Pinizzotto Center for Women’s Mental Health Massachusetts General Hospital Edmund and Carroll Carpenter Professor of Psychiatry Harvard Medical School www.mghcme.org Disclosures My spouse/partner and I have the following relevant financial relationship with a commercial interest to disclose: 12-Month Disclosure Research Support for the National Pregnancy Registry for Atypical Antipsychotics: Alkermes Biopharmaceuticals; Otsuka Pharmaceuticals; Sunovion Pharmaceuticals, Inc.; Teva Pharmaceuticals; Janssen Pharmaceutica ; Other research support: Brain & Behavior Research Foundation; JayMac Pharmaceuticals; National Institute on Aging; National Institutes of Health; SAGE Therapeutics Advisory/Consulting: Alkermes Biopharmaceuticals ,Praxis Precision Medicines, Inc.(through MGH Clinical Trials Network Initiative); Honoraria: None Royalty/patent, other income: None www.mghcme.org Reproductive Psychiatry and the COVID-19 Pandemic • Family planning and the pandemic • Telemedicine and implications for pregnancy and postpartum period • Infertility treatment and the pandemic • Perinatal anxiety during the COVID 19 crisis • Importance of euthymia during pregnancy • Reframing postpartum experience JAMA Psychiatry. Published online July 15, 2020. doi:10.1001/jamapsychiatry.2020.1947 https://womensmentalhealth.org/obgyn/reproductive-psychiatry-during-the-covid-19-pandemic/ www.mghcme.org3 Virtual Rounds at CWMH during COVID : Wednesdays at 2 PM https://womensmentalhealth.org/posts/resource-join-us-for-virtual-rounds-at-the-center-for-womens-mental-health-on-wednesdays/ www.mghcme.org Treatment considerations for women with MDD in pregnancy and the postpartum period • Depression during pregnancy is strongest predictor of postpartum depression • Nothing is more important maternal euthymia www.mghcme.org Major Depression During Pregnancy Are pregnant women protected against relapse or new onset of major depression? O’Hara et al. J Abnorm Psychol. 1990 Evans et al. BMJ. 2001 Yonkers et al. Epidemiology 2011 Roca et al. J Affective Disorders 2013 www.mghcme.org6 www.mghcme.org Time to Relapse in Patients Who Maintained or Discontinued Antidepressant 1 0.9 0.8 0.7 Maintained (N = 82) 0.6 0.5 0.4 0.3 Discontinued (N = 65) 0.2 0.1 Percentage of Patients Remaining Well 0 0 12 24 36 Gestational Age Cohen LS, et al. JAMA. 2006 www.mghcme.org8 Womensmentalhealth.org 9 www.mghcme.org Psychotropic Drug Use in Pregnancy • Medications used when risk to mother and fetus from disorder outweighs risks of pharmacotherapy • Optimum risk/benefit decision for psychiatrically ill pregnant women • Patients with similar illness histories make different decisions regarding treatment during pregnancy • No decision is risk-free • Collaborative, patient-centered approach required Henshaw Fam Plann Perspect. 1998 www.mghcme.org10 Treatment of Depression During Pregnancy: Lessons Learned and New Directions • Focus of concern regarding known and unknown risks of fetal exposure to psychiatric medications is increasingly balanced by data supporting risk of exposure to disorder, stress and HPA-axis dysregulation on fetoplacental unit • Enhanced appreciation for impact of disorder and chronic stress on long term behavioral outcomes www.mghcme.org11 Maternal Stress or Depression IN UTERO Programming of Fetal HPA Axis Dysregulation of the HPA Axis Dysregulation of HPA Axis Increased Elevated Elevated CRH Reactivity Cortisol Levels to Stress Increased Vulnerability to Mood and Anxiety Disorders www.mghcme.org www.mghcme.org 14 What is the Safest Antidepressant for Women of Childbearing Age? www.mghcme.org14 Phasing Out: FDA Pregnancy Categories • Category A: – Well controlled studies in human pregnancy show no increased risk to the fetus • Category B: – Animal studies show no increased risk to the fetus OR – Animal studies show an increased risk to the fetus but well controlled human studies do not. • Category C: – Animal studies show an increased risk to the fetus and there are no well controlled studies in human pregnancy OR – There aren’t any animal studies or well controlled human studies. www.mghcme.org http://womensmentalhealth.org/posts/fda-finalizes-guidelines-pregnancy-lactation-labeling-information/ www.mghcme.org Timeline to Changes in Product Labeling Required Submission Date of NDAs, BLA, ESs PLLR Format New Applications Submitted on or after 6/30/2015 At time of submission -------------------------------- PLLR Implementation Date (6/30/2015) -------------------------------- Approved 6/30/2001 to 6/29/2002 6/30/2018 Approved 6/30/2005 to 6/29/2007 Approved 6/30/2007 to 6/29/2015 6/30/2019 Or pending on 6/30/2015 Older Approved Applications Approved 6/30/2002 to 6/29/2005 6/30/2020 Not required to be in PLLR For applications approved prior to format. However, must 6/30/2001 in old format labeling remove Pregnancy Category by 6/29/2018 Do not distribute www.mghcme.org SSRI Use During Pregnancy • Recent findings and more data inform the pharmacologic treatment of depression during pregnancy – Consistent conclusions that the absolute risk of SSRI exposure in pregnancy is small1-3 – Consistent pattern of malformations with SSRI exposure is lacking – Case-control studies reveal inconsistent data regarding teratogenic risk of individual SSRIs4-9 Reproductive safety data on SSRIs exceed what is known about most other medicines used in pregnancy 1 Louik C et al. N Engl J Med 2007; 2 Einarson TR, Einarson A. Pharmacoepidemiol Drug Saf 2005; 3 Einarson A, et al. Am J Psychiatry 2008; 4 Alwan S, et al. N Engl J Med 2007; 5 Greene MF. N Engl J Med 2007; 6 Hallberg P, Sjoblom V. J Clin Psychopharmacol 2005; 7Wogelius P, et al. Epidemiology 2006; 8 www.gsk.ca/english/docs-pdf/PAXIL_PregnancyDHCPL_E-V4.pdf Dear Healthcare Professional (3/17/08); 9 www.fda.gov/medwatch/safety/2005/Paxil_dearhcp_letter.pdf Dear Healthcare Professional (3/17/08); Grigoriadis et al. J Clin Psychiatry 2013. www.mghcme.org18 Read our blog post on this topic: https://womensmentalhealth.org/posts/antidepressant-birth-defects/ Anderson KN, Lind JN, Simeone RM, Bobo WV, Mitchell AA, Riehle-Colarusso T, Polen KN, Reefhuis J. Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects. JAMA Psychiatry. 2020 Aug 5:e202453. Huybrechts KF, Palmsten K, Avorn J, Cohen LS, Holmes LB, Franklin JM, Mogun H, Levin R, Kowal M, Setoguchi S, Hernández-Díaz S. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014 Jun 19;370(25):2397-407. Wisner KL, Oberlander TF, Huybrechts KF. The Association Between Antidepressant Exposure and Birth Defects-Are We There Yet? JAMA Psychiatry. 2020 Aug 5. www.mghcme.org • No evidence of increased risk for major malformations or cardiovascular malformations in children of pregnant women exposed to SSRIs www.mghcme.org Cardiovascular Malformation and Fetal SSRI Exposure Huybrechts et al. NEJM 2014. www.mghcme.org “Poor Neonatal Adaptation” and SSRI Use During Pregnancy 22 • Consistent data: Late trimester exposure to SSRIs is associated with transient irritability, agitation, jitteriness, and tachypnea (25-30%) • Overall studies do not adequately control for maternal mental health condition, adequate blinding of exposure in neonatal assessments • Clinical implication: Should women be treated with antidepressants late in pregnancy and during labor and delivery (Warburton et al. 2010) • Are any subgroups of newborns vulnerable to enduring symptoms beyond the first days of life ? Levinson-Castiel R, et al. Arch Pediatr Adolesc Med. 2006 Chambers CD, et al. N Engl J Med. 2006 Chambers, BMJ, 2009 CWMH Blog, July 27 2005: http://womensmentalhealth.org/posts/neonatal-symptoms-after-in-utero-exposure-to-ssris/ www.mghcme.org22 What are the Long-term Neurobehavioral Effects of Prenatal Exposure to an Antidepressant? www.mghcme.org23 Full blog post: https://womensmentalhealth.org/posts/antidepressants-neurodevelopment/ Singal D, Chateau D, Struck S, Lee JB, Dahl M, Derksen S, Katz LY, Ruth C, Hanlon-Dearman A, Brownell M. In Utero Antidepressants and Neurodevelopmental Outcomes in Kindergarteners. Pediatrics. 2020 May;145(5). Andrade C. Genes as Unmeasured and Unknown Confounds in Studies of Neurodevelopmental Outcomes After Antidepressant Prescription During Pregnancy. J Clin Psychiatry. 2020 May 26;81(3):20f13463. Free Article Rommel AS, Bergink V, Liu X, Munk-Olsen T, Molenaar NM. Long-Term Effects of Intrauterine Exposure to Antidepressants on Physical, Neurodevelopmental, and Psychiatric Outcomes: A Systematic Review. J Clin Psychiatry. 2020 May 12;81(3):19r12965. Andrade C. Offspring Outcomes in Studies of Antidepressant-Treated Pregnancies Depend on the Choice of Control Group. J Clin Psychiatry. 2017 Mar;78(3):e294-e297. Free Article www.mghcme.org www.mghcme.org www.mghcme.org26 Treatment Guidelines Depression : Does Severity Drive Treatment Recommendations (and Patient Choice) • Psychotherapy: First-line for mild to moderate MDD • Lifestyle components: Nutrition, weight management, prenatal care ; treatment for co-morbid substance abuse • Evidence base for CBT , Behavioral Activation and MBCT (prevention) • Women trying to conceive who have histories of MDD: –Encourage period of euthymia –Sustained remission: consider tapering and discontinuing ? –More recently depressed or with symptoms: consider remaining on medication, optimizing medication • Pregnant
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